Computational Exploration of Potential Pharmacological Inhibitors Targeting the Envelope Protein of the Kyasanur Forest Disease Virus.

The limitations of the current vaccination strategy for the Kyasanur Forest Disease virus (KFDV) underscore the critical need for effective antiviral treatments, highlighting the crucial importance of exploring novel therapeutic approaches through in silico drug design. Kyasanur Forest Disease, caused by KFDV, is a tick-borne disease with a mortality of 3-5% and an annual incidence of 400 to 500 cases. In the early stage of infection, the envelope protein plays a crucial role by facilitating host-virus interactions. The objective of this research is to develop effective antivirals targeting the envelope protein to disrupt the virus-host interaction. In line with this, the 3D structure of the envelope protein was modeled and refined through molecular modeling techniques, and subsequently, ligands were designed via de novo design and pharmacophore screening, yielding 12 potential hits followed by ADMET analysis. The top five candidates underwent geometry optimization and molecular docking. Notably, compounds L4 (SA28) and L3 (CNP0247967) are predicted to have significant binding affinities of -8.91 and -7.58 kcal/mol, respectively, toward the envelope protein, based on computational models. Both compounds demonstrated stability during 200 ns molecular dynamics simulations, and the MM-GBSA binding free-energy values were -85.26 ± 4.63 kcal/mol and -66.60 ± 2.92 kcal/mol for the envelope protein L3 and L4 complexes, respectively. Based on the computational prediction, it is suggested that both compounds have potential as drug candidates for controlling host-virus interactions by targeting the envelope protein. Further validation through in-vitro assays would complement the findings of the present in silico investigations.

Statistical optimisation of protease production using a freshwater bacterium Chryseobacterium cucumeris SARJS-2 for multiple industrial applications.

Feathers, rich in keratin, are usually the unused by-products of poultry industries. In addition, the cast-off X-ray films serve as secondary sources of silver, and the traditional method of silver extraction from this source is costly and not eco-friendly. Therefore, the current study focuses on protease production using a freshwater bacterium Chryseobacterium cucumeris SARJS-2, aiming to convert these wastes into useful products. The protease production was optimized by one-factor-at-a-time (OFAT), followed by Plackett Burman design (PBD) and response surface methodology (RSM). The protease production got enhanced by more than two folds after the statistical optimisation. Upon partial purification, the enzyme activity increased by approximately three folds. The protease was active in the range of temperatures from 25 to 75 °C, but the optimum temperature was recorded as 35 °C. The protease exhibited detergent compatibility and organic solvent stability. The detergent compatibility suggests the protease could be a detergent additive. It was also found that the presence of Fe+2 enhanced protease activity. The protease was tested for stain removal, feather degradation and silver recovery applications. It was found that the protease could efficiently remove stains of blood and tomato sauce. In addition, the protease was found to be a successful candidate for feather degradation, thereby feather-hydrolysate production which has prominent roles as nature-friendly fertilizer and animal feed ingredient. The protease also degraded gelatin from the X-ray films to release the silver-halides for silver recovery. The results recommend that the SARJS-2 protease is a potential candidate for use in eco-friendly applications in various industrial sectors.